Hyperglycemic coma E14.01

Synonyms

Coma diabeticum; diabetic coma; hyperosmolar coma; hyperglycemic hyperosmolar nonketotic coma; ketoacidotic coma; nonketoacidotic coma; diabetic ketoacidosis; sugar shock;

First author

Records of Valentini dating from 1711 are found in which he described an apple or violet-like pervasive odor of the body and urine of a person suffering from diabetes mellitus, which most closely corresponds to the smell of acetone. Joseph Kaulich (1830 - 1886) confirmed this observation in 1860 and was the first to describe the clinical picture of acetonemia.

In 1842, William Prout (1785 - 1850) was the first to record all the symptoms of diabetic coma (Schadewaldt 1975).

In 1874 Adolf Kußmaul (1822-1902) was the first to describe the special respiration in coma diabeticum, which was later named after him and is known as Kußmaul respiration (Kluge 2003).

Hyperglycemic coma is a metabolic derailment caused by absolute and/or relative insulin deficiency, volume deficiency, and acid-base abnormalities (Kasper 2015), which is associated with serious complications (Kasper 2015) and leads to death if left untreated (Herold 2020).

The course of hyperglycemic coma varies: ketoacidotic coma (DKA = diabetic ketoacidosis [Kasper 2015]) or hyperosmolar com a (HHS = hyperglycemic hyperosmolar state [Kasper 2015]) may occur (Herold 2020).

• Ketoacidotic coma:

The incidence of DKA is estimated to be 6.4 - 14 cases per 100,000 population or 4.6 - 8 cases per 1,000 diabetic patients. In 20 - 30 % it is the first manifestation of DM (Mehnert 2003).

DKA occurs preferentially in type 1 DM, but can also occur in type 2, but then predominantly in patients of Hispanic or African American descent (Kasper 2015).

DKA is the most common coma, occurring in 80-90% of cases (Waldhäusl 2013).

• Hyperosmolar coma:

Less epidemiological data are available for HHS. It is estimated to be 10 - 15 % of the incidence of DKA. As the initial diagnosis of DM, HHS manifests in 30 - 40 % and is thus more frequent than in DKA (Mehnert 2003).

HHS occurs preferentially in type 2 DM (Kasper 2015) and accounts for approximately 10 - 20 % of all hyperglycemic comas (Waldhäusl 2013).

In about 30 % of patients with hyperglycemic coma, features of both diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome are found (Mehnert 2003).

The triggers of hyperglycaemic coma vary widely.

The most common cause is acute infection, accounting for about 40% (Herold 2020).

Other causes can be:

• insufficient exogenous insulin supply:
  • insufficientprescription of insulin
  • technical errors in the measurement or during injection
• lack of exogenous insulin supply:
  • first manifestation of a previously unknown diabetes mellitus
  • interruption of insulin administration with insulin pumps
  • incorrect storage of insulin (too hot or too cold)
  • inadequate treatment (tablets instead of insulin when insulin is needed)
  • omitted injection
  • defects of the pen (Herold 2020)
• increased insulin requirements:
  • accident
  • operation
  • gastrointestinal diseases
  • infections (urinary tract infection etc.)
  • dietary errors
  • Gravidity
  • Hyperthyroidism (Herold 2020)
  • Treatment with corticosteroids, saluretics (Herold 2020), beta-blockers (Ellinger 2007)
  • Acute myocardial infarction (Herold 2020)
  • stress (Ellinger 2007)
  • pancreatitis (Haak 2018)

• Ketoacidotic coma:

In DKA, both relative and absolute insulin deficiency are present. This leads to hepatic gluconeogenesis and lipolysis despite the elevated BG values. In the latter, ketone bodies such as acetone, acetoacetic acid and beta-hydroxybutyric acid are formed. The acids cause a drop in pH, increase the anion gap and lead to a consumption of bicarbonate (Reitgruber 2021).

• Hyperosmolar coma:

In HHS, there is decreased peripheral glucose utilization: Insulin deficiency causes increased glucose production by glycogenolysis and gluconeogenesis in the liver and impairs the utilization of glucose in skeletal muscle .

Hyperglycemia results in osmotic diuresis, leading to volume depletion intravascularly (Kasper 2015).

However, ketosis can be prevented by the small amounts of insulin still present, which cause an inhibition of lipolysis in adipose tissue (Herold 2020).

Diabetic decompensation is differentiated into three different clinical forms:

• 1. cardiovascular form:

Here there is, for example, a volume deficiency, shock, etc.

• 2. pseudoperitonitis form:

In this form, there are peritoneal irritation symptoms with gastric and intestinal atony (danger of gastric hyperinflation!).

• 3. renal form:

This leads to acute renal failure.

(Herold 2020)

Ketoacidotic coma develops very suddenly, in contrast to hyperosmolar coma, which shows an insidious onset (Herold 2020).

In diabetic ketoacidosis, one differentiates between different degrees of severity:

- mild: pH < 7.3 bicarbonate < 15 mmol / l

- moderate: pH < 7.2 bicarbonate < 10 mmol / l

- severe: pH < 7.1 bicarbonate < 5 mmol / l

(Herold 2020)

DKA:

In DKA, symptoms range from mild ketoacidotic metabolic derailment to life-threatening diabetic coma, with the severity of symptoms correlating with the severity of ketoacidosis (Haak 2018).

Symptoms may include:

• lack of appetite
• weight loss (due to diuresis, catabolism [Berndt 2015])
• reduced AZ
• general weakness
• dyspnea
• tachypnea (Reitgruber 2021)
• nausea
• Vomiting (the latter two caused by ketosis [Berndt 2015].
• Abdominal pain up to the so-called "pseudoperitonitis diabeticum".

This is not found in HHS (Reitgruber 2021). It is caused by hypokalemia and acidosis (Berndt 2015).

• Signs of dehydration such as:
  • detachable, standing skin folds
  • dry oral cavity (dehydration caused by osmotic diuresis [Berndt 2015])
  • Muscle cramps (caused by fluid and electrolyte loss [Berndt 2015]).
  • Blood pressure drop (also caused by fluid and electrolyte loss [Berndt 2015])
  • Polyuria (primary; caused by osmotic diuresis [Berndt 2015])
  • Oligo-anuria (secondary).
• Kussmaul resp iration to compensate for acidosis (not found in HHS [Reitgruber 2021]).
• Acetone odor of exhaled air (not found in HHS [Reitgruber 2021])
• Failure of reflexes
• Gastroparesis (caused by hyperglycemia [Berndt 2015]).

In the moderate severity of DKA, general drowsiness is added, which is accompanied by loss of consciousness in severe forms.

(Haak 2018)

HHS:

The above symptoms - with the exception of those typical of ketone bodies (such as acetone odor, pseudoperitonitis, etc.) can also occur in HHS.

Typical for HHS are:

• extremely high BG- value, usually > 600 mg / dl (Reitgruber 2021)
• tachycardia (due to vasodilation [Berndt 2015])
• Hypotension (Kasper 2015)

Gastrointestinal symptoms are found less frequently than in DKA (Mehnert 2003).

In addition to the above symptoms, symptoms of the precipitating disease such as apoplexy, myocardial infarction, pneumonia, sepsis, etc. may also be present (Kasper 2015).

Since the clinical symptoms are sometimes not always clear, sometimes the precipitating clinical picture such as infection, apoplexy, myocardial infarction, etc., is clinically leading (Haak 2018).

Physical examination

• Evidence of exsiccosis
• Tachypnea
• Tachycardia
• Acetone odor
• pseudoperitonitis symptoms

(Reitgruber 2021)

Glasgow Coma Scale

The severity of the disturbance of consciousness is determined with the Glasgow- Coma- Scale, where the score can range from 3 to 15 points (Herold 2020).

DKA is defined biochemically as:

• Blood glucose > 250 mg / dl (13.9 mmol / l)

plus

• Ketonemia

and / or

• Ketonuria

and / or

• arterial pH < 7.35

or

• venous pH < 7.3
• Serum bicarbonate < 270 mg / dl (15 mmol / l)

(Haak 2018)

Suspicious for DKA are:

• Ketone bodies in the urine or blood
• Hyperglycemia

If these values are pathological, it is recommended to determine the following values for further diagnosis:

• arterial and venous blood gas analysis
• blood count
• potassium
• serum creatinine
• CRP

In case of V. a. infections, blood cultures should also be taken ((Haak 2018)).

In hyperglycemic coma, there are:

• Hyperglycemia
• Glucosuria
• elevated Hb
• HKT elevated
• Leukocytosis
• Serum sodium normal to slightly decreased (Herold 2020)
• Serum ketones elevated (in DKA)
• Metabolic acidosis (in DKA)
• beta-hydroxybutyrate elevated (in DKA [Herold 2020])

In HHS, there may be metabolic acidosis with a small anion gap as a result of the increased lactic acid. Any moderate ketonuria is most likely indicative of a starvation state (Kasper 2015).

• Normal values are usually seen in:
  • Magnesium
  • Chloride
  • Phosphate (Kasper 2015).
• Serum potassium may be normal to elevated prior to initiation of insulin therapy (Herold 2020)
• Creatinine normal to slightly elevated (as a result of ketone bodies or exsiccosis [Reitgruber 2021]).

In addition to the above values and the internal medicine admission laboratory, the following should also be determined:

• Urine findings including drug test
• Autoantibodies IA2, GAD- 65 etc. in case of first manifestation of type 1 DM
• Blood alcohol level (Reitgruber 2021)

Certain (laboratory) results allow conclusions to be drawn about the nature of hyperglycaemic coma:

• Diabetic ketoacidosis

Blood glucose: > 250

Serum osmolarity

(mosmol / kg): variable

Serum HCO3 (mmol / l): < 15

Ketones in serum / urine: positive

anion gap: > 11

arterial pH: between < 7,1 to < 7,35

cerebral symptoms: awake to stupor / coma

• Hyperosmolar coma

blood glucose: > 600 (sometimes into the 4-digit range [Reitgruber 2021])

Serum osmolarity

(mosmol / kg): > 320

Serum HCO3 (mmol / l): > 15

Ketones in serum / urine: low

anion gap: variable

arterial pH: > 7,3

cerebral symptoms: stupor / coma

(Menche 2020)

In the case of sudden unconsciousness, differential diagnoses include:

• Cardiovascular e.g:
  • Shock
  • collapse
  • Adam Stokes seizure
  • Circulatory arrest
• Cerebral disorders e. g.:
  • subarachnoid hemorrhage
  • subdural / epidural hematoma
  • hypertonic mass hemorrhage
  • sinus thrombosis
  • meningitis
  • encephalitis
  • encephalomalacia
  • craniocerebral trauma
  • Epilepsy
  • generalized seizure
• Endocrine disorders e. g.:
  • hypoglycemic shock s. hypoglycemic coma (hypertonic muscles, skin moist, respiration normal etc.)
  • Coma diabeticum
  • Addison crisis
  • diabetes insipidus
  • pituitary coma
  • hypercalcemic crisis
  • thyrotoxic crisis
  • myxedematous coma
• Toxic e. g.:
  • exogenous poisoning by
    • alcohol
    • drugs, especially heroin
    • Psychotropic drugs
    • Sedatives
  • endogenous poisoning by
    • Coma hepaticum
    • Uremia
• Anoxemic e. g.:
  • Hypercapnia in respiratory global insufficiency
  • Asphyxiation

(Herold 2020)

• Lactic acidotic coma e. g.:
  • severe hypoxia
  • Leigh encephalopathy (rare [Danne 2016]).
  • NW of therapy with biguanides
  • Infusion with fructose in case of fructose intolerance
• Psychic e. g.:
  • Hysteria

[Herold 2020)

• acute abdomen (in the pseudoperitonitic form [Herold 2020])

DKA:

• venous thrombi
• acute respiratory distress syndrome
• cerebral oedema (often develops in children as DKA subsides; both the aetiology and treatment of cerebral oedema have not yet been clearly established)
• upper gastrointestinal hemorrhage (Kasper 2015)
• Hyperchloremic acidosis (due to excessive amounts of NaCl solution [Berndt 2015]).

HHS:

• Shock
• Sepsis
• thromboembolic events (Mehnert 2003)

Diabetic ketoacidosis:

Type 1 diabetics should be admitted to hospital immediately for intensive care if they are clinically suspected of having moderate or severe DKA. In the case of a mild form, outpatient treatment may be possible (Haak 2018).

Hyperosmolar hyperglycemic syndrome:

Intensive medical monitoring is also required in this case. Therapeutically, the treatment of the usually pronounced hyperglycemia, the life-threatening hypovolemia and the serum hyperosmolality are in the foreground. The hyperketonemia typical of DKA is not found (Haak 2018).

For intensive care therapy may be necessary:

• bladder catheter for balancing
• central venous catheter for CVD measurement
• Gastric tube for the pseudoperitonitis form (Herold 2020).

The following should be monitored:

• half-hourly:
  • Blood pressure
  • Heart rate (Haak 2018)
• hourly:
  • Blood glucose
• every 2 h:
  • Base excess
  • Bicarbonate
  • Sodium
  • Potassium
  • Glasgow Coma Scale
  • Blood gas analysis with pH- value (Herold 2020 / Haak 2018)

Prophylaxis required regarding:

• Thromboembolism
• Pressure ulcer
• Pneumonia (Herold 2020)

Diabetic ketoacidosis:

In DKA, the following therapeutic principles are recommended:

• Initial volume administration of 1 l of isotonic solution (e.g., 0.9% NaCl) within the first hour to stabilize the circulation. Subsequently, fluids and electrolytesshould be administered depending on concomitant diseases, age, height, and weight (administration of 6 l / 24 h may be required [Haak 2018]).

In patients with known heart failure, there is a risk of pulmonary edema due to too rapid infusion rate. Here, therefore, infusion should be slow (Herold 2020).

• Potassium:

Hypokalemia must be compensated for prior to insulin treatment, as potassium shifts it intracellularly, posing a risk of hypoglycemic ventricular fibrillation (Herold 2020).

- Substitution of potassium at a pH of > 7.1:

- for potassium > 4 - 5 mmol /l substitution of 10 - 15 mmol / l

- for potassium 3 - 4 mmol / l substitution of 15 - 20 mmol / l

- for potassium < 3 mmol / l substitution of 20 - 25 mmol / l (Herold 2020)

A maximum of 40 mmol of potassium chloride should be infused per 1,000 ml of NaCl 0.9% at a time (Haak 2018). Contraindication to potassium administration is anuria (Herold 2020).

If hypokalemia of < 3 mmol / l occurs during insulin therapy, insulin administration should be interrupted if necessary (Herold 2020).

The target serum potassium should be > 3.5 mmol / l (Kasper 2015).

• Administration of insulin via perfuser.

Insulin may act poorly in exsiccosis, so primary volume administration is required to achieve a good effect of insulin (Reitgruber 2021).

In shock, patients should be treated with normal insulin only; the duration of action is 20-40 min, and the half-life is <10 min (Herold 2020).

Blood glucose concentration should be reduced by 50 mg / dl / h (2.8 mmol / l), but not lower than 250 mg / dl during the first 24 h to avoid cerebral edema and retinal damage (Herold 2020).

From a blood glucose concentration of 300 mg / dl (16.7 mmol / l), an infusion with 10% glucose should run in parallel to avoid too rapid a drop in blood glucose (Haak 2018) and to avoid lipolysis with an increase in free fatty acids (Herold 2020).

"Low-dose" insulin therapy is recommended in most patients, i.e.:

- initial bolus of 0.10 - 0.15 IU / kg bw i. v. and subsequently about 5 IU normal insulin / h i. v. via the dosing pump (Herold 2020).

If blood glucose does not drop within 2 h, the patient requires higher doses of insulin due to insulin resistance. To break the resistance, the insulin dose should be doubled. In rare cases, an even higher amount of insulin may be needed beyond that (Herold 2020).

• Bicarbonate:

Bicarbonate should only be given from a pH- value < 7.0 and only until corrected to pH 7.1 (Haak 2018), since lipolysis is inhibited under insulin therapy anyway. The dosage should be only 25% of the calculated requirement to avoid hypokalemia (Herold 2020). Too high a dose of bicarbonate also increases the risk of cerebral edema (Kasper 2015).

• Sodium:

Sodium is substituted as part of infusion therapy (Herold 2020).

• Phosphate:

Phosphate is usually within the normal range. If the value is < 0.5 mmol / l, substitution of about 50 mmol / 24 h may be recommended. However, phosphate is contraindicated in renal insufficiency (Herold 2020).

• Magnesium:

Magnesium deficiency may occur during treatment of DKA, requiring appropriate substitution (Kasper 2015).

• Specific therapy such as antibiotics, etc.
• Research into the causes of coma (Haak 2018).

The complication rate can be reduced by:

- low-dose insulin therapy

- Slow compensation of metabolic derailments (Herold 2020).

Hyperosmolar hyperglycemic syndrome:

Treatment differs from the above in that initially no insulin is given. Volume replacement with 0.9% saline alone results in a decrease in blood glucose levels.

• Sodium:

Although there is hypernatremia due to exsiccosis, there is real sodium loss. Provided urine output is normal and there is only moderate hypernatremia of < 150 mmol / l, rehydration should be with 0.9% NaCl or Ringer's solution. If there is marked hypernatremia of > 150 mmol / l or if there is marked hyperosmolality, the use of semi-isotonic saline or hypoosmolar whole electrolyte solution (Herold 2020) is recommended.

The sodium concentration should not fall faster than 180 mg / dl (10 mmol / l) within 24 h (Haak 2018).

• Potassium:

The substitution of potassium is the same as in DKA (see above).

• Blood glucose:

Blood glucose should not drop more than 90 mg / dl (5 mmol / l) per hour.

If the BG does not drop further with i. v. administration of the fluid alone or there is ketonemia of > 18 mg / dl (1 mmol / l), insulin infusion of 0.05 IU / kg / h should be started (Haak 2018).

Kasper (2015) previously recommends an insulin bolus of 0.1 IU / kg bw.

The CNS needs some time to normalize the water shifts triggered by the coma. Therefore, the patient may remain unconscious despite normalization of blood glucose, electrolytes, pH and volume balance. This disturbance usually disappears with a delay (Herold 2020).

The diet should start with a light diet. A small amount of normal insulin s. c. should be injected before each meal. Subsequently, a readjustment of the DM is necessary (Herold 2020).

With appropriate, early therapy, the lethality of DKA is low and is < 1 %. It is more likely to be related to the triggering causes(myocardial infarction, infection, etc.) than to the DKA itself (Kasper 2015).

However, DKA remains the most common cause of death in diabetic children (Waldhäusl 2013).

The lethality of HHS ranges from 5 - 16 %. Causes of early mortality, estimated at around 15 %, are shock, sepsis or underlying disease. Late mortality (≥ 72 h) is often caused by thromboembolic events or consequences of treatment. In the case of HHS, more patients die from the disease causing the HHS than from the HHS itself (Mertens 2021).

Prophylaxis

Type 1 diabetics are recommended to perform regular test strip measurements to detect ketone bodies in the urine for prophylaxis of diabetic ketoacidotic coma (Haak 2018).

Diabetics should also be educated about the symptoms and precipitating factors of DKA, as well as behavior regarding diabetes mellitus. During illness or even when oral intake is impaired, the patient should:

- measure blood glucose frequently

- measure ketones in the urine as soon as the BG is > 300 mg / dl (16.5 mmol / l)

- drink plenty of fluids

- continue insulin administration

- consult a doctor as soon as:

- uncontrolled hyperglycaemia occurs

- persistent vomiting occurs

- in case of dehydration

(Kasper 2015)

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